Elevated insulin levels and insulin resistance in Pima Indian diabetics and nondiabetics suggest that cellular changes external to the panceras may be important in the pathogenesis of obesity and diabetes mellitus. The aim of this project is to study several aspects of insulin function in cells obtained from normal and diabetic Pima Indians, in order to determine if diabetes mellitus is expressed in genetic differences in insulin action at the cellular level. Fibroblast cultures have been established from normal and diabetic Pima Indians. Cellular metabolism and transport functions are being studied in the presence and absence of insulin, in order to define cell insulin action in this system, to determine if cellular abnormalities in insulin response occur in individuals with diabetes and to investigate factors which may induce cell insulin resistance. Stimulation of rapid metabolic effects by insulin and the insulin-like growth factor, MSA, are being compared to investigate the functional relationships between receptors for these peptide hormones in fibroblasts.